WHITTIER, Calif. — Lynn Whittaker stood in the hallway of her home looking at the framed photos on the wall. In one, her son Andrew is playing high school water polo. In another, he’s holding a trombone.

The images show no hint of his life today: the seizures that leave him temporarily paralyzed, the weakness that makes him fall over, his labored speech, his scrambled thoughts. Andrew, 28, can no longer feed himself or walk on his own. The past nine years have been a blur of doctor appointments, hospital visits, and medical tests that have failed to produce answers.

“You name it, he doesn’t have it,” his mother said.

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Andrew has never had a clear diagnosis. He and his family are in a torturous state of suspense, hanging their hopes on every new exam and evaluation.

Recently, they have sought help from the Undiagnosed Diseases Network, a federally funded coalition of universities, clinicians, hospitals, and researchers dedicated to solving the nation’s toughest medical mysteries. The doctors and scientists in the network harness advances in genetic science to identify rare, sometimes unknown, illnesses.

At the University of California, Los Angeles, one of the network’s sites, Andrew’s medical team would map his genetic makeup, then bring him in for a week of exams and consultations with specialists.

On a Monday morning in late January, Andrew and his parents were in an exam room at UCLA. Lynn teased her son, saying she was going to put him in a freezer until doctors figured out what was wrong.

“Then we’ll pull you back out again,” she said, smiling.

“I’ll never get pulled out,” Andrew responded.

“Yes, you will,” she said. “You will.”

Lynn Whittaker holds an old photograph of her son playing water polo.

A life-changing mystery

Andrew Whittaker’s odyssey began one afternoon at age 19, when he started trembling and couldn’t speak. Doctors suspected he was suffering from anxiety and prescribed medication to control it. But Andrew said he continued to have “episodes,” during which everything just went blank.

Andrew also started losing his balance and falling off his bicycle. The family visited several hospitals. Doctors discovered that the receptors in his brain were malfunctioning and that he lacked sufficient dopamine, a chemical compound in the body responsible for transmitting signals between nerve cells. As a result, Andrew has some symptoms similar to those of Parkinson’s disease. Doctors also confirmed he was having seizures.

One afternoon last fall at precisely noon, as Andrew sat propped up on the living room couch, Lynn’s phone alarm sounded, signaling it was time for his medication. Lynn pried open Andrew’s hand, which was clenched into a fist, and dropped in the pills.

To keep Andrew from falling, the family has lowered his bed and removed carpet from the house. They also bought him a wheelchair. Their precautions don’t always work. One morning, Lynn was in the kitchen when she heard a crash. “I ran in there and he’s laid flat on his back,” she said.

Andrew is close to his mom. But he also gets frustrated. He can’t shower or dress without her help. He’s had to give up the things he loved to do: printing T-shirts. Skateboarding. Shooting short films. He’s lost friends and can’t imagine dating anymore.

“Girlfriends? Forget about it,” he said, his face twitching as he talks. “They want a guy who can do stuff for them, not the other way around.”

Lynn gives Andrew his medicine.Heidi de Marco/KHN

Writing a new disease encyclopedia

The Undiagnosed Diseases Network was founded in 2015 with a $43 million grant from the National Institutes of Health. Building on work already being done at the NIH, the initiative expanded to include universities across the country: Duke, Columbia, and Stanford are among the other sites. The goals are to provide answers for patients with mysterious diseases and to learn more about the disorders.

A proposal last month by President Donald Trump to cut the NIH budget by $5.8 billion could put the program in jeopardy.

Even with the best technology and the finest brains at work, progress is slow. Since its launch, the network has received nearly 1,400 applications on behalf of patients. It has accepted 545 for review so far. Just 74 of the cases have been diagnosed, including 11 at UCLA. Andrew Whittaker’s case is among many in progress.

It’s like battling “an unknown enemy,” said Dr. Euan Ashley, one of the principal investigators of the network’s Stanford University site. “That is a particular form of torment that other patients don’t have.”

A diagnosis can end families’ painful odyssey while helping physicians and scientists better understand rare diseases and human physiology, said Rachel Ramoni, former executive director of the network, which is based at Harvard University.

Researchers throughout the network use advanced medical technology. For example, to study patients’ gene expression and disease progression, they can make models using nearly transparent zebrafish, whose genetic structure is similar to that of humans. And scientists can conduct whole genome sequencing, which allows the medical team to read a patient’s DNA and identify changes that can reveal what may be causing a disease.

“We have powerful techniques to look at every gene that is being expressed as well as every gene that is inherited,” said Dr. Stanley Nelson, one of UCLA’s principal investigators and the lead doctor on Andrew’s case. “This is an example of true precision medicine.”

Nelson said the network can examine all known genes — not just the ones believed to have mutations that cause diseases. Doing that can lead to the discovery of new illnesses.

“Part of what we have to do is keep building that library, that encyclopedia of what gene and what gene mutations cause what symptoms,” Nelson said. “It’s just incomplete at this moment.”

Already the work is helping patients and their families come to terms with their illnesses. In one case, at Stanford, a toddler was diagnosed with two rare diseases, including a connective tissue disorder called Marfan syndrome, after doctors conducted a form of sequencing that looks for changes in coded genetic segments known as exons.

“A lot of times your ability to be diagnosed depends on who is in the room,” Ramoni said. “And what we are doing with the network is we are expanding exponentially the number of people in the room.”

Doctors at one institution might think their patient is a unique case, only to learn that colleagues elsewhere have a patient with a similar illness. But even when diseases are diagnosed or gene mutations are discovered, treatments may still not be available.

Dr. Stanley Nelson performs various tests on Andrew during an appointment at UCLA.

Running the medical gauntlet

Nelson, Andrew’s main doctor, walked into the UCLA exam room at the beginning of the family’s week there. He told Andrew he’d read through the medical records. “We’re going to try to figure you out.”

The work Nelson does is personal. His teenage son, Dylan, has Duchenne muscular dystrophy, a genetic disorder that causes muscle degeneration and weakness. Nelson knows his son’s disease will eventually take his life, but he said having a diagnosis makes all the difference.

“My heart very much goes out to the families that don’t even get an adequate diagnosis,” he said.

He asked the Whittakers to describe their son’s journey and he conducted a short physical exam, asking Andrew to push against his hand and touch his own nose. Andrew trembled and his shoulders tensed, but he did it.

The rest of the week, Andrew underwent several other diagnostic tests, including a muscle biopsy, an EEG, MRI, and a lumbar puncture. He remained upbeat, though running the medical gauntlet clearly wore him out. He also met with UCLA specialists in brain degeneration and muscle and nerve disorders.

At week’s end, Nelson sat down with the family to explain what he’d found. He had reviewed Andrew’s genome and compared it with that of both parents. Andrew had one copy of a defective gene that leads to Parkinson’s but the genome sequencing didn’t show a second copy, without which it could not be Parkinson’s.

He also explained that Andrew’s illness was clearly progressive and that his brain was shrinking, making it harder for him to process language and information. Nelson said he still didn’t have a diagnosis — he believed it was a brand-new disease.

Nelson planned to continue poring over the test results, conducting additional exams, and communicating with others in the network. He also is analyzing Andrew’s muscle, skin, and blood to see whether any mutated gene is expressed abnormally.

Even in the absence of a clear diagnosis, Nelson said, rare diseases like Andrew’s help educate scientists and may help other patients. “These are the people we as a society will owe a great debt of gratitude,” he said. “They are effectively donating their lives to this process.”

Lynn Whittaker was disappointed. “We are still left with just hope that they will come up with something,” she lamented. “What else do we have?”

Andrew said his relatives have asked if he’s scared the doctors will find something. “I’m more scared if they don’t,” he replied.

Kaiser Health News, a nonprofit health newsroom whose stories appear in news outlets nationwide, is an editorially independent part of the Kaiser Family Foundation.

My nephew was diagnosed with the rare Kikuchi Disease. I am reaching out to find more information. He suffers everyday and doctors are trying to find the best solution.
Do you have any information, help or direction as to help with this disease
Thank you
Trish

Non-cancer related Whipple surgery 4 years ago. Very sick every since and getting worse. Major constipation all the time. Massive amount of miralax linzess and other 11 medications just to survive and doctors don’t want to try to find out what is wrong. I honestly feel like I will not live much longer and the doctors just don’t care.

Ok, this is going to be long and I don’t know if you can help. I have Graves Disease with hyperthyroidism, along with endometriosis, depression, low bone density, high blood pressure, severe migraines, and sleep deprivation. I can’t take otc pain meds because I’m allergic to IBUPROFEN and Tylenol/aspirin are not good with my other issues. My doctors keep adding meds to my list and seem to be refusing to help other than medicating me. I don’t know what to do and I feel like no one will listen to me. I would like them to preform a full hysterectomy (however because the endometriosis is not only in my uterus it won’t fully solve the issue) and my doctor stated he is worried about my bone density and my heart issue. I would like them to remove my thyroid to help with the Graves’ disease, however my doctor is trying to push me to do the radioiodine treatment and I don’t like the potential for cancer after that treatment. I just don’t know what to do, or where to start. I don’t want to be on all the medications I have and I really don’t want to live with the severe pain I feel like I’m always going through.

Hi. I have been experiencing fever of unknown origin for almost 2 yrs now. Every night I run a fever between 102 to 105. This will happen for at least 4 days to a week straight. Then I will skip a week or so and it repeats itself. I also have pain in the middle of my back down to my the front and back of my legs. The pain is excruciating. All of this started, after I had my Gall Bladder removed in Nov 2016. I have been seen at Ochsners New Oleans, Rheumatology, Hematology/Oncology, Gastro, Cardiology with every test coming back negative. I’ve even had a bone marrow biopsy and lumbar puncture. All negative. My blood work is never normal, however, no one can seem to tell me what’s wrong. If you could offer suggestions or point me in the direction of a somewhere I could be referred to, it would be greatly appreciated.

After having breast implants for 12 years, I suffered from a host of symptoms. I explanted in April of this year. However, some symptoms were immediately gone, others worsened and newer appeared. Lacunar Stroke Right Radiata for one. My balance, vision, worsened my BPPV which was a late diagnosis. I had baker Grade 4 capsular contracture with a rupture of the right implant. Mold and other debris can been seen floating in implants. My lymph nodes have been swollen for months. I told This is normal. Upon reading written reports there is nothing normal about my CT SCANS AND MRI! Is there anyone I can turn to that can look a the “ Whole Picture” that can help in my case?

My wife suffered through nearly the exact same syndrome related to breast implants. Implants were done by a world renowned plastic surgeon in California. Severe headaches, chest pain, fibrositis, etc. —saw experts around the USA for treatment. The implants ruptured in the first few years. My wife had surgical removal of implants and a abdominal transplant for breast restructuring by chief of plastic surgery at UCLA. My wife passed away recently, but I have kept all the records of her history, consults, and lab reports which if you have a serious need for the help you want and need, then I will forward the information etc. that you need to have available. You can contact me at cgg9232@gmail.com.

My son developed some similar symptoms that are undiagnosable by doctors and lab tests. Following increasing pain from headaches at age 43 to the point that he lost his job working as a computer data specialist. His MRI showed a brain mass, had neurosurgery, found a leaking Barrie aneurysm on Circle of Willis at base of brain and no tumors. Four stents were placed in the neck of the aneurysm by arteriogram hopefully to scar it enough to close the entrance into the aneurysm. Over the last 8 years he has tremors increasing, increased weakness, lost taste for food and stopped eating, lost 50 lbs to a rack of bones, mentally depressed, did not respond to Neurologists meds for seizures, lost balance and finally couldn’t walk without help, developed morning nausea and vomiting lasting 4 hours on empty stomach, headaches disabling, repeat MRI angioarteriography showed aneurysm-neck still open, blood lab essentially normal, his physicians gave up on treating him because of no diagnosis or response to meds, however Narco did help headaches.
Being a physician myself and forcing doctors to run all the tests, GI scoping -small ulcers duodenum, no cerebrospinal fluid drainage from nose, finally Scott was dying on floor from emaciation and admitted to hospital for 7 days with intensive care, nutrition fluids, nausea meds, and remarkably he rapidly improved enough to walk by himself. Interestingly, during all this process he remained mentally lucid and could carry on normal thinking and communications but still could not read without pain in head, could not legibly sign his name.
At home he improved physically, walking by himself, followup physical therapy, and good appetite with weight gain right away with minimal nausea and no vomiting. The doctors were amazed at how fast and how well he improved. They had labeled him a neurotic for lack of a true diagnosis and said all his symptoms were “mental”, however, that changed after his hospital recovery. There were lots of people praying for him and his recovery and certainly God may have had a lot to do with the recovery—-otherwise, how could anyone explain his recovery with just fluids and nutrition and counseling as therapy. We are a Christian family and seek God’s help often.
Scott previously was a second-degree “Tae Kwan Do” black belt with an IQ estimated at 147. On street drugs in teens, smoked, drank excessively. He has been street drug free for 12 years, still drank alcohol for headache pain relief when Narco didn’t stop headaches but now quit that completely, and will stop smoking soon because his doctors told him that cigarettes and alcohol will kill him otherwise.

My thought is that maybe one or more of Scott’s symptoms could be a major lead to a diagnosis of your son’s problem in some way. With the proven health value of Marijuana, that was a last resort we planned to try, but got well without that. Perhaps your son’s diagnosis could lie in an arterial malformation around the brain—has he had cerebral angiography?
Like my son, a leaky artery, affecting brain function, but small enough to be easily found. I ask myself, does the neurosurgery suction of blood clots result in all the symptoms Scott developed after the in and out operation—how could that gentle surgery account for all that stuff? How could insertion of 4 stents into the aneurysm opening cause all those symptoms?

I wish your son well. I will tell you that you must never give up seeing specialists or trying new meds, or treatments. Many of the newest medical treatments begin in Europe before we get them–primarily because there is no medical malpractice to deal with and more knowledge is found, more skills developed, and that also has increased health consequences to patients one should be aware of. You can’t sue the government that runs their healthcare system for those unexpected consequences to new ideas of treatment.

This had been similar to my life for the last 8 years. I’m about to see my 10th or so specialist and then my second rheumatologist. I’ve seen pulmonologist, psychiatrist, pain specialist, neurologist, and more. The hardest thing is that my primary care provider no longer has an interest in finding a definite diagnosis. Here’s settled in for Fibromyalgia even though I don’t meet the main criteria and exceed other parts. He told me to give up and accept it, but other doctors such as my neologist said it was not Fibro and to not give up. Luckily my insurance doesn’t require doctor referrals from my PCP for specialist so I can at least pursue answers on my own.